A clinical trial of chemotherapy given both prior to and after definitive local therapy is proposed. The study design incorporates stratification of patients by various risk factors and randomization to either receive definitive local therapy alone or accompanied by adjuvant chemotherapy. The chemotherapy consists of methotrexate prior to surgery and/or radiation therapy and adriamycin and cis-platinum following local treatment. The study has accrued 67 patients to date with no apparent differences between the treatment groups. The groups remain coded and the study continues to solicit new cases. Related laboratory investigation using the hemocytometer leukocyte adherence inhibition assay has demonstrated a high degree of site specificity of tumor associated reactivity by head and neck cancer patients.